Prognostic value and clinical impact of 18FDG-PET in the management of children with Burkitt lymphoma after induction chemotherapy.

Objective: Burkitt Lymphoma (BL) is a rare and aggressive form of B cell lymphoma that is curable using intensive chemotherapy. Obtaining a complete response (CR) at the end of induction chemotherapy is a major prognostic factor. This study retrospectively evaluates the potential impact of 18FDG-PET in the management of children with BL after induction chemotherapy, and the prognostic performance of the Deauville criteria.Methods: 19 children with BL treated according to the French LMB2001 protocol between 2005 and 2012 were included. 18FDG-PET and conventional imaging (CI) were performed after induction chemotherapy to confirm CR. 18FDG-PET was interpreted according to Deauville criteria with follow up and/or histology as the gold standard.Results: 18FDG-PET was negative in 15 cases, in agreement with CI in 9/15 cases. The six discordant cases confirmed to be negative by histology, were considered as true negative for 18FDG-PET. Negative predictive value (NPV) of CI and 18FDG-PET were 73 and 93% respectively. The five-year PFS was significantly higher in patients with negative 18FDG-PET than those with positive 18FDG-PET (p=0.011). Conclusion: 18FDG-PET interpreted using Deauville criteria can help confirm CR at the end of induction chemotherapy, with a prognostic impact on five-year PFS. Its high NPV could limit the use of residual mass biopsy. Given the small size of our population, these results need to be confirmed by future prospective studies on a larger population

Improvement of radioimmunotherapy using pretargeting

During the past two decades, considerable research has been devoted to radionuclide therapy using radiolabelled monoclonal antibodies and receptor binding agents. Conventional Radioimmunotherapy (RIT) is now an established and important tool in the treatment of hematologic malignancies such as Non-Hodgkin lymphoma. For solid malignancies, the efficacy of RIT has not been as successful due to lower radiosensitivity, difficult penetration of the antibody into the tumor and potential excessive radiation to normal tissues. Innovative approaches have been developed in order to enhance tumor absorbed dose while limiting toxicity to overcome the different limitations due to the tumor and host characteristics.Pretargeting techniques (pRIT) are a promising approach that consists of decoupling the delivery of a tumor monoclonal antibody (mAb) from the delivery of the radionuclide. This results in a much higher tumor-to-normal tissue ratio and is favorable for therapy as well and imaging. This includes various strategies based on avidin/streptavidin-biotin, DNA-complementary DNA and bispecific antibody-hapten bindings. PRIT continuously evolves with the investigation of new molecular constructs and the development of radiochemistry. Pharmacokinetics improve dosimetry depending on the radionuclides used (alpha, beta and Auger emitters) with prediction of tumor response and host toxicities. New constructs such as the Dock and Lock technology allow production of a variety of mABs directed against tumor-associated antigens. Survival benefit has already been shown in medullary thyroid carcinoma. Improvement in delivery of radioactivity to tumors with these pretargeting procedures associated with reduced hematologic toxicity will become the next generation of RIT. The following review addresses actual technical and clinical considerations and future development of pRIT

A pretargeting system for tumor PET imaging and radioimmunotherapy

International audienceLabeled antibodies, as well as their fragments and antibody-derived recombinant constructs, have long been proposed as general vectors to target radionuclides to tumor lesions for imaging and therapy. They have indeed shown promise in both imaging and therapeutic applications, but they have not fulfilled the original expectations of achieving sufficient image contrast for tumor detection or sufficient radiation dose delivered to tumors for therapy. Pretargeting was originally developed for tumor immunoscintigraphy. It was assumed that directly-radiolabled antibodies could be replaced by an unlabeled immunoconjugate capable of binding both a tumor-specific antigen and a small molecular weight molecule. The small molecular weight molecule would carry the radioactive payload and would be injected after the bispecific immunoconjugate. It has been demonstrated that this approach does allow for both antibody-specific recognition and fast clearance of the radioactive molecule, thus resulting in improved tumor-to-normal tissue contrast ratios. It was subsequently shown that pretargeting also held promise for tumor therapy, translating improved tumor-to-normal tissue contrast ratios into more specific delivery of absorbed radiation doses. Many technical approaches have been proposed to implement pretargeting, and two have been extensively documented. One is based on the avidin-biotin system, and the other on bispecific antibodies binding a tumor-specific antigen and a hapten. Both have been studied in preclinical models, as well as in several clinical studies, and have shown improved targeting efficiency. This article reviews the historical and recent preclinical and clinical advances in the use of bispecific-antibody-based pretargeting for radioimmunodetection and radioimmunotherapy of cancer. The results of recent evaluation of pretargeting in PET imaging also are discussed